N-(4-pyridyl or 4-quinolinyl) arylacetamide and 4-(aralkoxy or aralkylamino) pyridine pesticides

ABSTRACT

N-(4-Pyridyl or 4-quinolinyl) arylacetamides, for example N-((3-chloro-2-ethyl)-4-pyridyl)(4-(4-chlorophenoxy) phenyl)-acetamide, and 4-(aralkyoxy or aralkylamino)pyridines, for example 4-[2-[4-(2,2,2-trifluoroethoxy)phenyl]ethoxy]pyridine, are active against nematodes, insects, mites, and plant pathogens.

RELATED APPLICATIONS

This application is a continuation-in-part of Ser. No. 07/753,519, filedSep. 3, 1991, now abandoned.

FIELD OF THE INVENTION

This invention provides new compounds that are useful as nematicides,insecticides, miticides, and plant fungicides. The invention alsoprovides nematicidal, insecticidal, miticidal, and fungicidal methods.

There is an acute need for new nematicides, insecticides, miticides, andplant fungicides. Available nematicides typically have high mammaliantoxicity and must be used at high rates. A nematicide that can beapplied at lower rates and that has lower mammalian toxicity wouldrepresent a significant advance.

Mites and insects are developing resistance to the miticides andinsecticides in current use. Resistance to insecticides in anthropods iswidespread, with at least 400 species resistant to one or moreinsecticides. The development of resistance to some of the olderinsecticides, such as DDT, the carbamates, and the organophosphates iswell known. But resistance has even developed to some of the newerpyrethroid insecticides and miticides. Similarly, target pathogens arerapidly developing resistance to currently used fungicides. At least 50species of fungi have developed resistance to the benzimidazolefungicides. Even recently introduced fungicides, like the acylalanines,which initially exhibited excellent control of potato late blight andgrape downy mildew in the field, have become less effective because ofresistance. Therefore a need exists for new insecticides, miticides, andfungicides, and particularly for compounds that have new or atypicalmodes of action.

SUMMARY OF THE INVENTION

This invention provides compounds of the formula (1): ##STR1## andN-oxides and salts thereof, wherein

R is H, (C₁ -C₄)alkyl, or benzyl;

R¹, R², R³, and R⁴ are one of the following:

a) R³ and R⁴ are H, and R¹ and R² are independently halo, (C₁ -C₄)alkyl,halo (C₁ -C₄)alkyl, (C₃ -C₄) branched alkyl, (C₃ -C₇)cycloalkyl, (C₁-C₄)alkoxy, or halo(C₁ -C₄)alkoxy;

b) one of R¹, R², R³, and R⁴ is (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl,(C₁ -C₄) alkoxy, halo (C₁ -C₄) alkyl, halo(C₁ -C₄)alkoxy, (C₁ -C₄)alkylthio, (C₁ -C₄) alkylsulfinyl, (C₁ -C₄) alkylsulfonyl, aryl, orsubstituted amino, and the rest are H;

c) R¹, R², R³, and R⁴ are independently H or halo; or

d) R¹ and R² combine to form a (C₅ -C₆) saturated or unsaturatedcarbocyclic ring that is optionally substituted with one or two groupsselected from halo, (C₁ -C₄)alkyl, (C₃ -C ₄) branched alkyl, halo(C₁-C₄)alkyl, (C₃ -C₇)cycloalkyl, (C₁ -C ₄)alkoxy, halo (C₁ -C₄)alkoxy, orNO₂, and R³ and R⁴ are H;

R⁵ is H, (C₁ -C₄) alkyl or (C₁ -C₄) acyl;

R⁶ and R⁷ are independently (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl,phenyl, or substituted phenyl;

Y'Z together form a C₄ -C₁₁ saturated or unsaturated hydrocarbon chain,straight chain or branched, optionally including a hetero atom selectedfrom O, NR⁵, S, SO, SO₂, or SiR⁶ R⁷, where R⁵, R⁶, and R⁷ are as definedabove, and optionally substituted with one or more groups independentlyselected from (C₁ -C₄) alkyl, (C₂ -C₄) alkenyl, (C₂ -C₄) alkynyl,branched (C₃ -C₇) alkyl, (C₃ -C₇) cycloalkyl, (C₃ -C₇) cycloalkenyl,halo, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, hydroxy, or (C₁ -C₄)acyl; or

Y' is bond or a bivalent hydrocarbon radical one to five carbon atomslong, optionally substituted with (C₁ -C₄) alkyl, (C₂ -C₄) alkenyl (C₂-C₄) alkynyl, branched (C₃ -C₇) alkyl, (C₃ -C₇) cycloalkyl or (C₃ -C₇)cycloalkenyl, halo, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, hydroxy,CN, or (C₁ -C₄) acyl; and

Z is

(a) aryl or

(b) (C₃ -C₈) cycloalkyl or cycloalkenyl, optionally substituted with oneor more groups independently selected from (C₁ -C₄) alkyl, (C₁ -C₄)alkoxy, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, halo, hydroxy, or (C₁-C₄) acyl; where

aryl is

(a) a phenyl group optionally substituted with one or more groupsindependently selected from:

halo,

I,

(C₃ -C₈) cycloalkyl,

(C₃ -C₈) cycloalkenyl,

phenoxy,

substituted phenoxy,

phenylthio,

substituted phenylthio,

phenyl,

substituted phenyl,

NO₂, ##STR2## where R⁸ is (C₁ -C₇) alkyl halo (C₁ -C₇) alkyl, (C₃ -C₇)branched alkyl, halo (C₃ -C₇) branched alkyl, (C₃ -C₇) cycloalkyl, halo(C₃ -C₇) cycloalkyl, (C₁ -C ₇) alkoxy, phenyl, or substituted phenyl,acetoxy, OH, CN,

SiR⁹ R¹⁰ R¹¹ or OSiR⁹ R¹⁰ R¹¹, where R⁹ , R¹⁰ and R¹¹ are independently(C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl, or substituted phenyl,

NR¹² R¹³, where R¹² and R¹³ are independently H, (C₁ -C₄) alkyl, or (C₁-C₄) acyl,

S(O)R¹⁴, or SO₂ R¹⁴, where R¹⁴ is (C₁ -C₁₀) alkyl, phenyl, orsubstituted phenyl;

a C₁ -C₁₂ saturated or unsaturated hydrocarbon chain, straight chain orbranched optionally including a hetero atom selected from O, S, SO, SO₂,NR⁵, or SiR⁶ R⁷, where R⁵, R⁶ and R⁷ are as defined above, andoptionally substituted with halo, halo (C₁ -C₄) alkoxy, hydroxy, (C₃-C₈) cycloalkyl or cycloalkenyl, (C₁ -C₄) acyl, phenoxy, substitutedphenoxy, phenyl, substituted phenyl, phenylthio, or substitutedphenylthio;

(C₁ -C₇) alkoxy optionally substituted with halo, phenyl, substitutedphenyl, (C₃ -C₈) cycloalkyl or cycloalkenyl, phenoxy, or substitutedphenoxy;

(C₁ -C₇) alkylthio optionally substituted with halo, phenyl, substitutedphenyl, (C₃ -C₈) cycloalkyl or cycloalkenyl, phenoxy or substitutedphenoxy;

(b) a furyl group of formula (3) ##STR3## where R¹⁵ is H, halo,halomethyl, CN, NO₂, (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl,(C₁ -C₄) alkoxy, halo (C₁ -C₄) alkoxy;

(c) a thienyl group of the formula (4) ##STR4## where R¹⁶ is H, halo,halomethyl, CN, NO₂, (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl,(C₁ -C₄) alkoxy, halo (C₁ -C₄) alkoxy or thienyl;

(d) a group of formula (5) or (6) ##STR5## where R¹⁵ is as defined inparagraph (b), J is N or CH, and G is O, NR¹⁷, or S, provided that if Jis not N then G is NR, where R¹⁷ is H, (C₁ -C₄) alkyl, (C₁ -C₄) acyl,phenylsulfonyl, or substituted phenylsulfonyl;

(e) a group selected from optionally substituted naphthyl,dihydronaphthyl, tetrahydronaphthyl, and decahydronaphthyl;

optionally substituted indolyl; 1,3 -benzodioxolyl;2,6-dimethyl-4-morpholinyl; and 1-adamantyl;

(f) a group of the formula ##STR6## wherein m is 4; R²⁰ areindependently H, halo, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy,NO₂, CN, lower alkyl carbonyl, phenoxy, or substituted phenoxy, providedthat at least two of R²⁰ are selected from H and F; and Het is pyridyl,pyrazinyl, pyrimidinyl, or pyridazinyl, optionally substituted with oneor more groups selected from halo, lower alkyl, lower alkoxy, haloalkyl,haloalkoxy, NO₂, CN, and lower alkyl carbonyl;

(g) a group of the formula ##STR7## one of X² and X³ is N and the otheris CH;

R²¹ is --Z--R²², phenyl, or substituted phenyl;

Z is O or S; and

R²² is (C₁ -C₄) alkyl, (C₃ -C₇) branched alkyl, halo (C₁ -C ₇) alkyl,halo (C₃ -C₇) branched alkyl, (C₁ -C₄) alkoxy substituted (C₁ -C₄)alkyl, or naphthyl or phenyl, either of which may optionally besubstituted with up to three groups selected from halo, (C₁ -C₁₀) alkyl,branched (C₃ -C₇) alkyl, halo(C₁ -C₇) alkyl, hydroxy (C₁ -C₇) alkyl, (C₁-C₄) alkoxy, halo (C₁ -C₄) alkoxy, phenoxy, substituted phenoxy, phenyl,substituted phenyl, CN, NO₂, OH, (C₁ -C₄) alkanoyloxy, or benzyloxy.

The invention also provides new compounds of the formula (1A): ##STR8##and N-oxides and salts thereof, wherein

R¹, R², R³, and R⁴ are one of the following:

a) R³ and R⁴ are H, and R¹ and R² are independently halo, (C₁ -C₄)alkyl,halo(C₁ -C₄)alkyl, (C₃ -C₄) branched alkyl, (C₃ -C₇)cycloalkyl, (C₁-C₄)alkoxy, or halo(C₁ -C₄)alkoxy;

b) one of R¹, R², R³, and R⁴ is (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl,(C₁ -C₄) alkoxy, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, (C₁ -C₄)alkylthio, (C₁ -C₄) alkylsulfinyl, (C₁ -C₄) alkylsulfonyl, aryl, orsubstituted amino, and the rest are H; or

c) R¹, R², R³, and R⁴ are independently halo or H;

X is O, S, or NR⁵ ;

R⁵ is H, (C₁ -C₄) alkyl or (C₁ -C₄) acyl;

R⁶ and R⁷ are independently (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl,phenyl, or substituted phenyl;

YZ together form a C₅ -C₁₂ saturated or unsaturated hydrocarbon chain,straight chain or branched, optionally including a hetero atom selectedfrom O, NR⁵, S, SO, SO₂, or SiR⁶ R⁷, where R⁵, R⁶, and R⁷ are as definedabove, and optionally substituted with one or more groups independentlyselected from (C₁ -C₄) alkyl, (C₂ -C₄) alkenyl, (C₂ -C₄) alkynyl,branched (C₃ -C₇) alkyl, (C₃ -C₇) cycloalkyl, (C₃ -C₇)cycloalkenyl,halo, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, hydroxy, or (C₁ -C₄)acyl; or

Y is a bond or a bivalent hydrocarbon radical one to six carbon atomslong, optionally substituted with one or more groups independentlyselected from (C₁ -C₄) alkyl, (C₂ -C₄) alkenyl or (C₃ -C₇) alkynyl,branched (C₃ -C₇) alkyl, (C₃ -C₇) cycloalkyl (C₃ -C₇) cycloalkenyl,halo, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, hydroxy, or (C₁ -C₄)acyl; and

z is

(a) aryl or

(b) (C₃ -C₈) cycloalkyl or cycloalkenyl, optionally substituted with oneor more groups independently selected from (C₁ -C₄) alkyl, (C₁ -C₄)alkoxy, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, halo, hydroxy, or (C₁-C₄) acyl; where

aryl is

(a) a phenyl group optionally substituted with one or more groupsindependently selected from:

halo,

I,

(C₃ -C₈) cycloalkyl,

(C₃ -C₈) cycloalkenyl,

phenoxy,

substituted phenoxy,

phenylthio,

substituted phenylthio,

phenyl,

substituted phenyl,

NO₂, ##STR9## where R⁸ is (C₁ -C₇) alkyl halo (C₁ -C₇) alkyl, (C₃ -C₇)branched alkyl, halo (C₃ -C₇) branched alkyl, (C₃ -C₇) cycloalkyl, halo(C₃ -C₇) cycloalkyl, (C₁ -C ₇) alkoxy, phenyl, or substituted phenyl,acetoxy, OH, CN,

SiR⁹ R¹⁰ R¹¹ or OSiR⁹ R¹⁰ R¹¹, where R⁹, R¹⁰ and R¹¹ are independently(C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl, or substituted phenyl,

NR¹² R¹³, where R¹² and R¹³ are independently H, (C₁ -C₄) alkyl, or (C₁-C₄) acyl,

S(O)R¹⁴, or SO₂ R¹⁴, where R¹⁴ is (C₁ -C₁₀) alkyl, phenyl, orsubstituted phenyl;

a C₁ -C₁₂ saturated or unsaturated hydrocarbon chain, straight chain orbranched optionally including a hetero atom selected from O, S, SO, SO₂,NR⁵, or SiR⁶ R⁷, where R⁵, R⁶ and R⁷ are as defined above, andoptionally substituted with halo, halo (C₁ -C₄) alkoxy, hydroxy, (C₃-C₈) cycloalkyl or cycloalkenyl, (C₁ -C₄) acyl, phenoxy, substitutedphenoxy, phenyl, substituted phenyl, phenylthio, or substitutedphenylthio;

(C₁ -C₇) alkoxy optionally substituted with halo, phenyl, substitutedphenyl, (C₃ -C₈) cycloalkyl or cycloalkenyl, phenoxy, or substitutedphenoxy; or

(C₁ -C₇) alkylthio optionally substituted with halo, phenyl, substitutedphenyl, (C₃ -C₈) cycloalkyl or cycloalkenyl, phenoxy or substitutedphenoxy;

(b) a furyl group of formula (3) ##STR10## where R¹⁵ is H, halo,halomethyl, CN, NO₂, (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl,(C₁ -C₄) alkoxy, or halo (C₁ -C₄) alkoxy;

(c) a thienyl group of the formula (4) ##STR11## where R¹⁶ is H, halo,halomethyl, CN, NO₂, (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl,(C₁ -C₄) alkoxy, halo(C₁ -C₄) alkoxy, or thienyl;

(d) a group of formula (5) or (6) ##STR12## where R¹⁵ is as defined inparagraph (b), J is N or CH, and G is O, NR¹⁷, or S, provided that if Jis not N then G is NR, where R¹⁷ is H, (C₁ -C₄) alkyl, (C₁ -C₄) acyl,phenylsulfonyl, or substituted phenylsulfonyl;

(e) a group selected from

optionally substituted naphthyl, dihydronaphthyl, tetrahydronaphthyl,and decahydronaphthyl;

optionally substituted pyridyl;

optionally substituted indolyl; 1,3 -benzodioxolyl;2,6-dimethyl-4-morpholinyl; and 1-adamantyl.

The invention also provides a method of inhibiting a nematode populationwhich comprises applying to the locus of a nematode, a nematodeinactivating amount of a compound of the formula (1) or (1A) as definedabove.

The invention also provides a method of inhibiting an insect or mitepopulation which comprises applying to the locus of the insect orarachnid an effective insect or mite inactivating amount of a compoundof formula (1) or (1A).

The invention also provides a method of inhibiting plant pathogens whichcomprises applying an effective amount of a compound of formula (1) or(1A) to a locus of the pathogen.

DETAILED DESCRIPTION OF THE INVENTION

Throughout this document, all temperatures are given in degrees Celcius,and all percentages are weight percentages unless otherwise stated.

The term "halo" refers to a F, Cl, or Br atom.

The terms "alkoxy", "haloalkyl", "alkylsulfinyl", and "alkylsulfonyl"refer to straight chain and branched chain groups.

The terms "substituted phenyl", "substituted phenoxy", "substitutedphenylthio", and "substituted phenylsulfonyl", refer to such groupswherein the phenyl ring is substituted with up to three groupsindependently selected from halo, I, (C₁ -C₁₀) alkyl, branched (C₃ -C₆)alkyl, halo (C₁ -C₇) alkyl, hydroxy (C₁ -C₇) alkyl, (C₁ -C₇) alkoxy,halo (C₁ -C₇) alkoxy, phenoxy, substituted phenoxy, phenyl, substitutedphenyl, NO₂, OH, CN, (C₁ -C₄) alkanoyl, benzoyl, (C₁ -C₄) alkanoyloxy,(C₁ -C₄)alkoxycarbonyl, phenoxycarbonyl, or benzoyloxy.

The terms "substituted naphthyl", and "substituted indolyl" refer tothese ring systems substituted with one or more groups independentlyselected from halo, halo (C₁ -C₄) alkyl, CN, NO₂, (C₁ -C₄) alkyl, (C₃-C₄) branched alkyl, phenyl, (C₁ -C₄) alkoxy, or halo (C₁ -C₄) alkoxy.

The term "carbocyclic ring" refers to a saturated or unsaturatedcarbocyclic ring containing five or six carbon atoms.

The term "unsaturated hydrocarbon chain" refers to a hydrocarbon chaincontaining one or more sites of unsaturation.

The term "HPLC" refers to a high pressure liquid chromatography.

The term "bivalent hydrocarbon radical" refers to bivalent radicalsderived from normal alkanes by removal of hydrogen atoms from each ofthe two terminal carbon atoms of the chain, e.g. methylene, ethylene,trimethylene, tetramethylene, etc.

The term "substituted amino" refers to an amino group that issubstituted with one or two (C₁ -C₄) alkyl groups or one (C₁ -C₄)alkanoyl group.

The term "lower alkyl" refers to C1 to C6 straight hydrocarbon chainsand C3 to C6 branched and cyclic hydrocarbon groups.

The terms "lower alkenyl" and "lower alkynyl" refer to C2 to C6 straighthydrocarbon chains and C3 to C6 branched hydrocarbon groups containingat least one unsaturated bond.

The terms "lower alkoxy" and "lower alkylthio" refer to O-lower alkyland S-lower alkyl groups.

The term "haloalkyl" refers to lower alkyl groups substituted with oneor more halo atoms.

The term "haloalkoxy" refers to lower alkoxy groups substituted with oneor more halo atoms.

Unless otherwise indicated, when it is stated that a group may besubstituted with one or more substituents selected from an identifiedclass, it is intended that the substituents may be independentlyselected from the class.

PREFERRED EMBODIMENTS

Preferred compounds of formulas (1) and (1A) include the followingclasses:

a) compounds of formulas (1) wherein Y is --CH₂ -- and compounds offormula (1A) wherein Y' is --CH₂ CH₂ --;

b) compounds of formulas (1) and (1A) wherein Z is phenyl;

c) compounds of formulas (1) and (1A) wherein Z is a substituted phenylgroup as defined in paragraph (a) of the foregoing definition of "aryl;"

d) compounds of formulas (1) and (1A) wherein Z is a phenyl groupsubstituted with a (C₂ -C₄) alkoxy group;

e) compounds of formulas (1) and (1A) wherein Z is a phenyl groupsubstituted with a (C₃ -C₇)branched alkoxy group;

f) compounds of formulas (1) and (1A) wherein Z is a phenyl groupsubstituted with a halo (C₂ -C₄) alkoxy group;

g) compounds of formulas (1) and (1A) wherein Z is a phenyl groupsubstituted with a halo (C₃ -C₇)branched alkoxy group;

h) compounds of formulas (1) and (1A) wherein Z is a phenyl groupsubstituted with a phenoxy or substituted phenoxy group;

i) compounds of any of the foregoing groups c) to h) wherein the phenylgroup is monosubstituted in the 4-position;

j) compounds of formulas (1) and (1A) wherein R¹ is (C₁ -C₄) alkyl andR² is halo;

l) compounds of formulas (1) and (1A) wherein R¹ is ethyl and R² ischloro;

m) compounds of formula (1) wherein R¹ and R² combine to form ##STR13##i.e. compounds of the formula (12): ##STR14## where Y' and Z are asdefined above for formula (1), n is 1 or 2, R are independently selectedfrom halo, (C₁ -C₄)alkyl, (C₃ -C₄) branched alkyl, halo (C₁ -C₄)alkyl,(C₃ -C₇)cycloalkyl, (C₁ -C₄)alkoxy, halo (C₁ -C₄)alkoxy, or NO₂, and R³and R⁴ are H;

n) compounds as defined in foregoing paragraph m) wherein n is O or n is1 and R is 8-fluoro.

o) compounds of formulas (1) and (1A) wherein Z is a group of theformula ##STR15##

SYNTHESIS

The compounds of this invention are made using well known chemicalprocedures. The required starting materials are commercially available,or they are readily synthesized using standard procedures.

Compounds of Formula (1) can be prepared using the process illustratedin the following scheme: ##STR16## In this procedure, an acid derivative(8) in CH₂ Cl₂ is mixed, at room temperature, with an equimolar amountof the 4-aminopyridine derivative (7). To this solution, an equimolaramount of 1,3-dicyclohexyl-carbodiimide is added. The mixture is stirredabout 20 hours, then filtered. The residue is taken up in methylenechloride and filtered again to remove any residual 1,3-dicyclohexylurea.

Compounds of formula (1) can also be prepared using the proceduresillustrated in the following schemes 2 and 3. ##STR17##

In the procedure illustrated in Scheme 2, a slight excess of oxalylchloride is added dropwise to a solution of the carboxylic acid (8) in asuitable organic solvent, such as THF, methylene chloride, or xylenes,under nitrogen, at room temperature. The mixture may also include 1-2equivalents of pyridine or triethylamine. After stirring the mixture for30 minutes to 2 hours, the amine, in solution in a suitable organicsolvent, such as THF, methylene chloride, or xylene, is added dropwise.The mixture is heated to reflux for 8 to 24 hours, then allowed to coolto room temperature and partitioned between 1N sodium hydroxide andethyl ether. The aqueous phase is extracted with ethyl ether. Thecombined organics are washed with water and saturated sodium chloridesolution, then dried, filtered, and concentrated. ##STR18##

In the procedure illustrated in Scheme 3, an acid lo derivative (8) isheated to reflux in excess thionyl chloride for about two hours. Theexcess thionyl chloride is then removed by reducing pressure. To theresidue is then added a solution of the aminopyridine (7), andoptionally about two equivalents of triethylamine, in a suitable organicsolvent, such as acetonitrile, toluene, or xylene. The mixture is heatedto reflux for 8 to 24 hours, then allowed to cool to room temperatureand partitioned between 1N sodium hydroxide and ethyl ether. The aqueousphase is extracted with ethyl ether. The combined organics are washedwith water and saturated sodium chloride solution, then dried, filtered,and concentrated.

Compounds of formula (7) can be prepared using known procedures. Forexample, the preparation of 2-alkyl-4-amino3-bromopyridine and2-alkyl-4-amino-3-chloropyridine derivatives is described in J. Med.Chem. vol. 32, pages 1970-77 (1989). J. Prakt. Chem., vol 331, pages369-374 (1989) describes bromination of aminopicolines, affording otheruseful starting materials. Compounds of formula (7) can also be made byreduction of the corresponding azides by procedures similar to J. Prakt.Chem., vol 327, pages 521-522 (1985), as illustrated in Preparation 2hereinafter.

Carboxylic acid derivatives of formula (8) wherein Z is phenyl orsubstituted phenyl can be prepared using the known proceduresillustrated below in Scheme 4. Carboxylic acid derivatives of formula(8) wherein Z is a group of the formula ##STR19## can be prepared usingan analogous procedure. Carboxylic acid derivatives of formula (8)wherein z is a group of the formula ##STR20## can be prepared byreacting p-hydroxyphenyl acetic acid with the appropriatechloro-substituted heterocyclic compound, as illustrated hereinafter inPreparation 3.

Synthesis of Compounds of Formula (1A) Wherein X is O or S

The compounds of formula (1A) wherein X is O can be made, for example,by condensing a compound of formula (9) ##STR21## where R¹, R², R³, andR⁴ are as defined above for formula (1A) and L is a leaving group suchas F, Cl, Br, I, NO₂, 1,2,4-triazol-1-yl, OSi(CH₃)₃, arylthio, (C₁ -C₄)alkylthio, (C₁ -C₄) alkylsulfonyl, arylsulfonyl, alkoxy, orarylsulfonyl, with an alcohol or phenol of the formula (10):

    HO--Y--Z                                                   (10)

where Y and Z are as previously defined. The term "aryl" as used in thisparagraph refers, for example, to phenyl and substituted phenyl, e.g.4-nitrophenyl.

The reaction is preferably carried out in the presence of a strong base,such as sodium hydride, in a non-reactive organic solvent, such as DMF,at a temperature in the range of 0° to 25° C.

Compounds wherein X is S are made by the same procedure using analogousmercaptans of formula HS--Y--Z.

Starting materials of formula (9) are prepared using well knownprocedures, for example those described in the following European PatentApplications: EPA 326,330 (corresponding to allowed U.S. patentapplication Ser. No. 07/334,422, filed Apr. 7, 1989), and EPA 326,331(corresponding to U.S. Pat. No. 5,114,939).

Synthesis of Compounds of Formula (1A) Wherein x is NR⁵

Compounds of formula (1A) wherein X is NR⁵ and R⁵ is H or C₁ -C₄ alkylcan be prepared, for example, by aminating a suitably substitutedintermediate of the formula (9). For example, a chloride of formula (9)wherein L is Cl may be reacted with an amine of the formula (11)

    R.sup.5 'NH--Y--Z                                          (11)

where R⁵ ' is H or C₁ -C₄ alkyl and Y and Z are as previously defined,at a wide variety of temperatures (20°-180° C.), preferably in thepresence of an acid acceptor, such as triethylamine. The reaction may becarried out neat, or in a non-reactive organic solvent.

Alcohols of formula (10) and amines of formula (11) are also readilyprepared using conventional procedures, for example the classicchain-lengthening procedure illustrated in the following Scheme 4:##STR22## In step 1, KOH hydrolysis of the nitrile produces thecorresponding carboxylic acid. In step 2, lithium aluminum hydridereduction of the carboxylic acid produces the alcohol. Alternatively,the alcohol can be obtained by sodium borohydride reduction of thecorresponding aldehyde. The halogenation illustrated in step 3 may be,for example, chlorination with thionyl chloride. Treatment of the halidewith NaCN in step 4 gives the nitrile. Step 5 is a lithium aluminumhydride reduction of the nitrile using a Lewis acid such as H₂ SO₄ orAlCl₃. In step 6, hydrolysis of the nitrile gives the phenylacetic acidderivative (a compound of formula (8)), which is reduced to thephenethyl alcohol in step 7 using lithium aluminum hydride or otherconventional reducing agents.

Alternatively, and preferably, amines of formula (1A) are prepared inaccordance with the following reaction scheme: ##STR23##

In this procedure the amide of formula (1) is dissolved in THF and addeddropwise to a rapidly stirred suspension of lithium aluminum hydride(two fold molar excess) in THF at room temperature. Once the addition iscomplete, the reaction mixture is heated to reflux. The course of thereaction can be followed by TLC analysis. Once the reaction is complete,the mixture is cooled in an ice bath and quenched by the dropwiseaddition of saturated ammonium chloride, followed by 15% sodiumhydroxide. The resulting mixture is then filtered and the phasesseparated. The aqueous phase is extracted with ethyl ether. The combinedorganics are then dried, filtered, and concentrated.

The N-oxides and salts of compounds of formula (1) and (1A) are obtainedin the usual way.

EXAMPLES

The following tables identify compounds of formula (1) and (1A) thatwere prepared by the processes illustrated in the foregoing schemes.Detailed examples illustrating preparation of exemplary compounds followthe tables.

                                      TABLE I                                     __________________________________________________________________________     ##STR24##                                   (1)                              Compound                                                                            Y'   Z                  R.sup.1                                                                          R.sup.2                                                                          R.sup.3                                                                          R.sup.4                                                                          MP °C.                       __________________________________________________________________________     1    CH.sub.2                                                                            ##STR25##         H  H  H  H  104-105                              2    CH.sub.2                                                                            ##STR26##         H  H  H  H  oil                                  3    CH.sub.2                                                                            ##STR27##         H  H  H  H  107                                  4    CH.sub.2                                                                            ##STR28##         H  H  H  H  145                                  5    CH.sub.2                                                                            ##STR29##         H  H  H  H   87                                  6    CH.sub.2                                                                            ##STR30##         H  H  H  H  120                                  7    CH.sub.2                                                                            ##STR31##         H  H  H  H   60                                  8    CH.sub.2                                                                            ##STR32##         H  H  H  H  148                                  9    CH.sub.2                                                                            ##STR33##         H  H  H  H                                      10    CH.sub.2                                                                            ##STR34##         CH.sub.3                                                                         CH.sub.3                                                                         H  H   92                                 11    CH.sub.2                                                                            ##STR35##         CH.sub.3                                                                         CH.sub. 3                                                                        H  H  148                                 12    CH.sub.2                                                                            ##STR36##         CH.sub.3                                                                         CH.sub.3                                                                         H  H  146                                 13    CH.sub.2                                                                            ##STR37##         CH.sub.3                                                                         H  H  H  <50                                 14    CH.sub.2                                                                            ##STR38##         H  H  Cl CH.sub. 3                                                                        152                                 15    CH.sub.2                                                                            ##STR39##         F  F  F  F  138                                 16    CH.sub.2                                                                            ##STR40##         H  H  H  C.sub.2 H.sub.5                                                                  wax                                 17    CH.sub.2                                                                            ##STR41##         H  Cl Cl CH.sub.3                                                                         139                                 18    CH.sub.2                                                                            ##STR42##         H  H  Cl C.sub.2 H.sub.5                                                                  oil                                 19    CH.sub.2                                                                            ##STR43##         H  H  Cl C.sub.2 H.sub.5                                                                  121                                 20    CH.sub.2                                                                            ##STR44##         H  H  Cl C.sub.2 H.sub.5                                                                   98                                 21    CH.sub.2                                                                            ##STR45##         H  H  Cl C.sub.2 H.sub.5                                                                  107                                 22    CH.sub.2                                                                            ##STR46##         H  H  Cl C.sub.2 H.sub.5                                                                  104                                 23    CH.sub.2                                                                            ##STR47##         H  H  Cl C.sub.2 H.sub.5                                                                   90                                 24    CH.sub.2                                                                            ##STR48##         H  H  Cl C.sub.2 H.sub.5                                                                  102                                 25    CH.sub.2                                                                            ##STR49##         H  H  Cl C.sub.2 H.sub.5                                                                   92                                 26    CH.sub.2                                                                            ##STR50##         H  H  Cl H   88                                 27    CH.sub.2                                                                            ##STR51##         H  H  CH.sub.3                                                                         H  58-61                               28    CH.sub.2                                                                            ##STR52##         CH.sub.3                                                                         H  CH.sub.3                                                                         H  122                                 29    CH.sub.2                                                                            ##STR53##         H  H  Cl C.sub.2 H.sub.5                                                                  63-66                               30    CH.sub.2                                                                            ##STR54##         H  H  Cl C.sub.2 H.sub.5                                                                  72-74                               31    CH.sub.2                                                                            ##STR55##         H  H  Cl C.sub.2 H.sub.5                                                                   75                                 32    CH.sub.2                                                                            ##STR56##         H  H  Cl C.sub.2 H.sub.5                                                                  102                                 33    CH.sub.2                                                                            ##STR57##         H  H  Cl C.sub.2 H.sub.5                                                                  166                                 34    CH.sub.2                                                                            ##STR58##         H  H  Cl C.sub.2 H.sub.5                                                                    101.3                             35    CH.sub.2                                                                            ##STR59##         CH.sub.3                                                                         H  H  CH.sub.3                                                                          56                                 36    CH.sub.2                                                                            ##STR60##         H  H  Cl C.sub.2 H.sub.5                                                                   96                                 37    CH.sub.2                                                                            ##STR61##         H  H  Cl C.sub.2 H.sub.5                                                                  120-122                             38    CH.sub.2                                                                            ##STR62##         H  H  Br C.sub.2 H.sub.5                                                                  73-75                               39    CH.sub.2                                                                            ##STR63##         H  H  Cl C.sub.2 H.sub.5                                                                  140-141                             40    CH.sub.2                                                                            ##STR64##         H  H  Cl C.sub.2 H.sub.5                                                                  102-103                             41    CH.sub.2                                                                            ##STR65##         H  H  H  C.sub.2 H.sub.5                                                                  132-133                             42    CH.sub.2                                                                            ##STR66##         H  H  H  C.sub.2 H.sub.5                                                                  105-106                             43    CH.sub.2                                                                            ##STR67##         H  H  H  C.sub.2 H.sub.5                                                                  117-119                             44    CH.sub.2                                                                            ##STR68##         H  H  Cl C.sub.2 H.sub.5                                                                  119-120                             45    CH.sub.2                                                                            ##STR69##         H  H  Cl C.sub.2 H.sub.5                                                                  112-114                             46    CHCH.sub.3                                                                         (CH.sub.2).sub.7 CH.sub.3                                                                        H  H  Cl C.sub.2 H.sub.5                                                                  52-53                               47    CH.sub.2                                                                            ##STR70##         H  H  Cl C.sub.2 H.sub.5                                                                  117-119                             48    CH.sub.2                                                                            ##STR71##         H  H  Cl C.sub.2 H.sub.5                                                                  84-86                               49    CH.sub.2                                                                            ##STR72##         H  H  Cl C.sub.2 H.sub.5                                                                  139                                 50    CH.sub.2                                                                            ##STR73##         H  H  Cl C.sub.2 H.sub.5                                                                  oil                                 51    CH.sub.2                                                                            ##STR74##         H  H  Cl C.sub.2 H.sub.5                                                                  oil                                 52    CH.sub.2                                                                            ##STR75##         H  H  Cl C.sub.2 H.sub.5                                                                  152-154                             53    CH.sub.2                                                                           (CH.sub.2).sub.5 CH.sub.3                                                                        H  H  Cl C.sub.2 H.sub.5                                                                  58-60                               54    CH.sub.2                                                                           (CH.sub.2).sub.7 CH.sub.3                                                                        H  H  Cl C.sub.2 H.sub.5                                                                  63-65                               55    CH.sub.2                                                                           (CH.sub.2).sub.9 CH.sub.3                                                                        H  H  Cl C.sub.2 H.sub.5                                                                  78-80                               __________________________________________________________________________

                                      TABLE II                                    __________________________________________________________________________     ##STR76##                            (12)                                    Compound                                                                            Y' Z                 R  R.sup.3                                                                          R.sup.4                                                                          MP° C.                             __________________________________________________________________________    56    CH.sub.2                                                                          ##STR77##        8-F                                                                              H  H  167-169                                   57    CH.sub.2                                                                          ##STR78##        8-F                                                                              H  H  168-170                                   58    CH.sub.2                                                                          ##STR79##        8-F                                                                              H  H  glass                                     59    CH.sub.2                                                                          ##STR80##        8-F                                                                              H  H  169                                       60    CH.sub.2                                                                          ##STR81##        H  H  CH.sub.3                                                                         128-130                                   61    CH.sub.2                                                                          ##STR82##        H  H  H  165-167                                   62    CH.sub.2                                                                          ##STR83##        8-F                                                                              H  H  123-125                                   63    CH.sub.2                                                                          ##STR84##        8-F                                                                              H  H  oil                                       64    CH.sub.2                                                                          ##STR85##        8-F                                                                              H  H  145-147                                   65    CH.sub.2                                                                          ##STR86##        8-F                                                                              H  H  110-112                                   __________________________________________________________________________

                                      TABLE III                                   __________________________________________________________________________     ##STR87##                                (1A)                                Com-                                                                          pound                                                                             X  Y   Z                 R.sup.1                                                                          R.sup.2                                                                          R.sup.3                                                                         R.sup.4                                                                          MP° C.                         __________________________________________________________________________     1A O  (CH.sub.2).sub.2                                                                   ##STR88##        H  H  H H  oil                                    2A O  (CH.sub.2).sub.2                                                                   ##STR89##        H  H  H H  oil                                    3A O  (CH.sub.2).sub.2                                                                   ##STR90##        H  H  H H  oil                                    4A O  (CH.sub.2).sub.2                                                                   ##STR91##        H  H  H H  oil                                     5A                                                                              O  (CH.sub.2).sub.2                                                                   ##STR92##        H  H  H H  55-58                                  6A O  (CH.sub.2).sub.2                                                                   ##STR93##        H  H  H H  oil                                    7A O  (CH.sub.2).sub.2                                                                   ##STR94##        H  H  H H                                         8A O  (CH.sub.2).sub.2                                                                   ##STR95##        H  H  H H  oil                                    9A O  (CH.sub.2).sub.2                                                                   ##STR96##        H  H  H H  oil                                   10A O  (CH.sub.2).sub.2                                                                   ##STR97##        H  H  H H  oil                                   11A NH (CH.sub.2).sub.2                                                                  phenyl            H  H  H H  86-88                                 12A NH (CH.sub.2).sub.2                                                                   ##STR98##        H  H  H H  104-105                               13A NH (CH.sub.2).sub.2                                                                   ##STR99##        H  H  H H  oil                                   14A NH (CH.sub.2).sub.2                                                                   ##STR100##       H  H  H H  62                                    15A NH (CH.sub.2).sub.2                                                                   ##STR101##       H  H  H H  140                                   16A NH (CH.sub.2).sub.2                                                                   ##STR102##       H  H  H H  oil                                   17A NH (CH.sub.2).sub.2                                                                   ##STR103##       H  H  H H  oil                                   18A NH (CH.sub.2).sub.2                                                                   ##STR104##       H  H  H H  oil                                   19A NH (CH.sub.2).sub.2                                                                   ##STR105##       H  H  H H  118-119                               20A NH (CH.sub.2).sub.2                                                                   ##STR106##       H  H  H H  108-109                               21A O  (CH.sub.2).sub.2                                                                  2-naphthyl        H  H  H H  oil                                   22A O  (CH.sub.2).sub.2                                                                   ##STR107##       H  H  H H  oil                                   23A O  (CH.sub.2).sub.2                                                                   ##STR108##       H  H  H H  35.2                                  24A NH (CH.sub.2).sub.2                                                                   ##STR109##       CH.sub.3                                                                         H  H CH.sub.3                                 25A NH (CH.sub.2).sub.2                                                                   ##STR110##       CH.sub.3                                                                         CH.sub.3                                                                         H H                                        26A NH (CH.sub.2).sub.2                                                                   ##STR111##       CH.sub.3                                                                         CH.sub.3                                                                         H H  221                                   __________________________________________________________________________

The compounds were characterized by ¹ H NMR. All values were determinedin CDCl₃ and recorded as ∂ (ppm).

    ______________________________________                                        Compound                                                                      No.     Analysis                                                              ______________________________________                                        1A      3.09(t, 2H), 4.2(t, 2H), 6.72-7.59(m, 10H),                                   8.38 (m, 2H)                                                          2A      3.10(t, 2H), 4.20(t, 2H), 6.77(d, 2H), 7.1-7.31                               (m, 4H), 8.41(d, 2H)                                                  3A      1.40(t, 3H), 3.03(t, 2H), 4.02(q, 2H), 4.15                                   (t, 2H), 6.78(d, 2H), 6.84(d, 2H), 7.16(d,                                    2H), 8.39(d, 2H)                                                      4A      1.31(s, 9H), 3.08(t, 2H), 4.20(t, 2H), 6.77                                   (d, 2H), 7.22(d, 2H), 7.36(d, 2H), 8.43(d,                                    2H)                                                                   6A      2.33(s, 3H), 3.07(t, 2H), 4.17(t, 2H), 6.77                                   (d, 2H), 7.17(m, 4H), 8.39(d, 2H)                                     7A      0.27(s, 9H), 3.11(t, 2H), 4.22(t, 2H), 6.79                                   (d, 2H), 7.27(d, 2H), 7.49(d, 2H), 8.41(d,                                    2H)                                                                   8A      3.17(t, 2H), 4.26(t, 2H), 6.84(d, 2H), 7.22                                   (d, 2H), 7.35(d, 2H), 8.47(d, 2H)                                     9A      1.33(s, 9H), 3.06(t, 2H), 4.20(t, 2H),                                        6.77-7.17(m, 6H), 8.41(d, 2H)                                         10A     3.06(t, 2H), 4.17(t, 2H), 4.34(m, 2H),                                        6.91-6.76(m, 4H), 7.21(d, 2H), 8.40(d, 2H)                            13A     1.24(d, 6H), 2.2(1H), 2.8(q, 2H), 3.4(m,                                      3H), 6.46(t, 2H), 7.13(d, 2H), 7.16(d,                                        2H), 8.16(t, 2H)                                                      16A     .089(t, 3H), 1.3-1.6(m, 6H), 2.58(t, 2H),                                     2.88(t, 2H), 3.41(m, 1H), 4.3(bs, 1H), 6.42                                   (d, 2H), 7.1-7.3(m, 4H), 8.17(d, 2H)                                  17A     2.87(t, 2H), 3.39(td, 2H), 4.33(q, 2H),                                       6.41(d, 2H), 6.90(d, 2H)7.15(d, 2H), 8.16                                     (d, 2H)                                                               18A     3.05(t, 2H), 3.46(td, 2H), 4.7(bs, 1H),                                       6.48(d, 2H), 7.2-7.4(m, 4H), 8.15(d, 2H)                              24A     7.3-6.9(m, 9H), 6.17(s, 2H, pyridyl), 4.45(bs,                                1H, NH), 3.41(td, 2H), 2.89(t, 2H), 2.39(s,                                   6H, CH.sub.3 's)                                                      25A     8.10(d, 1H, J=6, 0 Hz, pyridyl H-6), 7.4-6.9                                  (m, 9H, phenyl), 6.43(d, 1H, J=6.0 Hz, pyridyl                                H-5), 4.1(bs, 1 H, NH), 3.46(td, J=6.9, 6.6                                   Hz, C .sub.--H.sub.2 NH), 2.94(t, 2H, J=7.2 Hz, C .sub.--H.sub.2              CH.sub.2 N),                                                                  2.48(s, 3H, CH.sub.3), 1.95(s, 3H, CH.sub.3)                          ______________________________________                                    

EXAMPLE 1 N-(4-pyridyl)-4-biphenylacetamide (Compound 4) ##STR112##

To a solution of 0.941 g (10 mmol) of 4-aminopyridine and 2.123 g of4-biphenylacetic acid in 50 mL of methylene chloride was added 2.063 gof 1,3-dicyclohexylcarbodiimide. After stirring the mixture at roomtemperature for about 24 hours, the mixture was filtered andconcentrated. The residue was taken up in methylene chloride, filteredand lo concentrated to give 2.997 g of a flaky, light green solid. Thiswas recrystallized from hexane/ethylacetate and vacuum oven dried togive 2.138 g of a light green solid. Yield 74%. M.P. 145.3° C.

EXAMPLE 2 N-(3-chloro-2-ethyl-4-pyridyl)(4-isopropylphenyl)acetamide(Compound 23) ##STR113##

Oxalyl chloride (0.48 mL, 5.50 mmol) was added to a solution of4-isopropylphenyl acetic acid (0.935 g, 5.25 mmol) in 20 mL of xylene atroom temperature. After the mixture was stirred for about 15 minutes,0.8 mL of pyridine was added. The mixture was stirred for an additional30 minutes, after which 4-amino-3-chloro-2-ethylpyridine (0.783 g., 5.00mmol) was added, and the resultant mixture was heated to reflux. Afterrefluxing for about 17 hours, the mixture was allowed to cool to roomtemperature and partitioned between 1N NaOH (75 mL) and ethyl ether (75mL). The aqueous phase was extracted with ethyl ether (75 mL). Thecombined organics were washed with water (1×100 mL), saturated NaCl(1×100 mL), and then dried, filtered, and concentrated to give 1.71 g.of a brown oil. The oil was chromatographed on silica gel, eluting with80% hexane/20% EtOAc. Isolation of the major product gave 0.391 g. ofthe desired compound as a solid. M.P. 90° C.

EXAMPLE 3 N-(3-chloro-2-ethyl-4-pyridyl) (4-((4-(trifluoromethyl)phenyl)oxy)phenyl)acetamide (Compound 34) ##STR114##

A mixture of (4-((4-(trifluoromethyl)phenyl)oxy)phenyl) acetic acid(1.05 g, 3.5 mmol) and 20 mL of thionyl chloride was heated to reflux.After refluxing two hours, the excess thionyl chloride was removed byreducing pressure. The residue was then treated with a solution of4-amino-3-chloro-2-ethylpyridine and 1 mL of triethylamine in 20 mL ofacetonitrile. The mixture was heated and allowed to reflux for about 24hours, then cooled to room temperature and partitioned between 1N NaOH(75 mL) and ethyl ether (75 mL). The aqueous phase was extracted withethyl ether (75 mL). The combined organics were washed with water (1×75mL), saturated NaCl (1×75 mL), and then dried, filtered, andconcentrated to give 1.32 g. of a yellow oil. The was chromatographed onsilica gel, eluting with 80% hexane/20% EtOAc. Isolation of the majorproduct gave 0.202 g. of the desired compound as a solid. M.P. 101.3° C.

Preparation 1 4-Azido-8-fluoroquinoline

A mixture of 2.08 g (0.0114 mol) of 4-chloro-8-fluoroquinoline, 1.12 g(0.0172 mol) of sodium azide, and 4.10 g ((0.0127 mol) of tetrabutylammonium bromide in 70 mL of dichloromethane and 25 mL of water wasrefluxed overnight. The layers were then separated and the organic layerwas washed once with water, passed through phase separating paper, andconcentrated to an oil, which was triturated with ether. The solid wasfiltered and the filtrate was concentrated to give 2.0 g of the titleproduct.

Preparation 2 4-Amino-8-fluoroquinoline

To a solution at 15°-20° C. of 4-azido-8-fluoroquinoline in 12 mL ofabsolute ethanol was added a portion of 0.57 g (0.015 mol) of sodiumborohydride. A powerful exotherm with vigorous evolution of gas wasobserved. The solution was cooled in ice and the remainder of thehydride was added in small portions within five minutes. The ice bathwas then removed. After about two hours, the mixture was poured intoabout 200 mL of ice water. The precipitate was collected and air driedovernight. Yield 1.35 g. M.P. 184°-186° C.

EXAMPLE 4 N-(8-fluoro-4-quinolinyl) (4-((4-chlorophenyl)oxy)phenyl)acetamide (Compound 59) ##STR115##

A mixture of 0.63 g (0.0024 mol) of (4-(4-chlorophenyl)oxy)phenylaceticacid and excess (10 mL) of thionyl chloride was refluxed for two hours.Excess thionyl chloride was then removed by reducing pressure, theresidue was taken up in xylene and 0.39 g (0.0024 mol) of4-amino-8-fluoroquinoline was added. The mixture was refluxed overnight.The xylene was removed by reducing pressure, then the residue was takenup in methylene chloride and the resulting mixture was washed once withwater and once with 0.1N sodium hydroxide. The pH of the aqueous layerwas adjusted to 7, and product was extracted with ethyl acetate. Themethylene chloride and ethyl acetate layers were combined and dried,concentrated to an oil. NMR indicated that the product was a mixture ofthe starting acid and the desired product. The product was taken up inmethylene chloride, washed with base (0.1N sodium hydroxide), dried, andconcentrated to an oil. This was chromatographed 100% CH₂ Cl₂ →10% CH₂Cl₂ /EtOAc in 2%/liter increments, and 0.14 g of the title product wascollected. This was mixed with hexane and filtered, giving a light brownsolid. Yield 0.13 g. M.P. 169° C.

Preparation 3 4-(3-chloro-6-pyridazinyloxy)phenylacetic Acid

To a mixture of 0.54 g (0.013 mol, 2.0 equiv) of 60% sodiumhydride/mineral oil dispersion in 10 m of dry DMF was added dropwise atroom temperature a solution 1.02 g (0.0067 mol) of the phenylacetic acidin 2.3 mL of DMF. After 15-20 minutes, a solid existed which wasdifficult to stir. The pyridazine (1.0 g, 0.0067 mol) was then added andthe mixture was heated at 60°-65° C. for about 2 hours and was allowedto cool. The mixture was poured onto ice water and was adjusted to pH 5with 2.0N HCl, and the precipitate was collected. This material wastriturated under heptane to afford 880 mg of the title product. MP124°-127° C.

EXAMPLE 1A 4-[2-[4-[4-(trifluoromethyl)phenoxy]phenyl]ethoxy]pyridine(Compound 1A)

To a suspension of 0.2 g of 60% NaH (as an oil dispersion, 0.005 m) in 5mL of DMF was added 1.41 g (0.005 m) of2-[4-[4-(trifluoromethyl)phenoxy]phenyl]ethanol. The mixture was stirredat room temperature for 30 minutes, until hydrogen evolution ceased. Tothe mixture was then added 0.79 g (0.005 m) of4-(methylsulfonyl)pyridine, and the mixture was stirred overnight atroom temperature. Excess DMF was then removed in vacuo. The resultingmaterial was diluted with water, and the product was extracted into CH₂Cl₂. The CH₂ Cl₂ layer was separated and filtered through phaseseparating paper, then concentrated. The residue was adsorbed ontosilica gel and chromatographed, eluting with CH₂ Cl₂ →30% EtOAc/CH₂ Cl₂.The resulting material was rechromatographed over fine-particle silicagel, eluting with CH₂ Cl₂ →50% EtOAc/CH₂ Cl₂. Yield 0.5 g.

EXAMPLE 2A 4-[2-[4-(1,1-dimethylethoxy)phenyl]ethoxy]pyridine (Compound9A)

To a suspension of about one-half gram of 60% NaH (dispersion in oil) in10 mL of dry DMF was added 1.5 g (0.0077 m) of2-[4-(1,1-dimethylethoxy)phenyl]ethanol. The mixture was stirred in awarm water bath until hydrogen evolution ceased. After 30-40 minutes, 1g (0.0064 m) of 4-(methylsulfonyl)pyridine in 5-7 mL of DMF was added.The mixture was stirred at room temperature overnight, then diluted withwater. The product was extracted into CH₂ Cl₂, and the extracts werewashed with saturated brine, filtered through phase separating paper,and concentrated in vacuo. The resulting material was azeotroped withxylene to remove excess DMF. This material was adsorbed onto silica geland chromatographed over silica gel 60 (230-400 mesh) using CH₂ Cl₂ →50%EtOAc/CH₂ Cl₂ to give the title product as an oil. Yield 0.7 g.

EXAMPLE 3A 4-[2-[4-(2,2,2-trifluoroethoxy)phenyl]ethoxy]pyridine(Compound 10A)

To a suspension of about one gram of 60% NaH (dispersion in oil) in 20mL of dry DMF was added 5.2 g (0.023 m) of2-[4-(2,2,2-trifluoroethoxy)phenyl]ethanol. The mixture was stirred atroom temperature for 40 minutes, then 3.1 g (0.02 m) of methylsulfonylpyridine was added. The mixture was stirred at room temperatureovernight, then DMF was evaporated in vacuo, and the residue was dilutedwith water and extracted with CH₂ Cl₂. The CH₂ Cl₂ layer was separated,washed with saturated NaCl solution and filtered through phaseseparating paper. The product was concentrated to yield 6.2 g of crudeproduct, which was adsorbed onto silica gel and chromatographed oversilica gel 60 (230-400 mesh) using CH₂ Cl₂ →50% EtOAc/CH₂ Cl₂ to givethe title product as an oil. Yield 2.5 g.

EXAMPLE 4A N-(2-Phenylethyl)-4-pyridinamine (Compound 11A)

A mixture composed of 2.0 g (0.0176 m) of 4-chloropyridine and 4.3 g(0.0352 m) of phenethylamine was heated under nitrogen to 160°-165° C.for one hour. The mixture was then cooled and 200 mL of a 50/50 mixtureof ammonium hydroxide in water was added. The product was extracted intoCH₂ Cl₂, which was then concentrated to dryness. The resulting materialwas purified by HPLC on silica gel, eluting with ethyl acetate toprovide 0.560 g of the title product.

EXAMPLE 5A N-[2-(4-biphenylyl)ethyl]pyridin-4-amine (Compound 15A)

A solution of 1.495 g (5.2 mmol) of N-(4-pyridyl)-4-biphenyl-acetamidein 30 mL of THF was added dropwise to a rapidly stirred suspension of0.49 g of lithium aluminum hydride (13 mmol) in 30 mL of THF at roomtemperature. Once the addition was complete, the mixture was heated toreflux and was refluxed for approximately 17 hours. The mixture was thencooled in an ice bath and quenched by the dropwise addition of 30 mL ofsaturated ammonium chloride followed by 2 mL of 15% sodium hydroxide.The mixture was filtered and the phases separated. The aqueous phase wasextracted with ethyl ether (2×75 mL). The combined organic phases werethen dried, filtered, and concentrated to give 1.68 g of a yellow solid.This was chromatographed on silica gel, eluting with 90% CHCl₃ /10% CH₃OH. Removal of solvent left 1.20 g. of a light yellow solid. This wasrecrystallized from hexane/ethyl acetate and vacuum oven dried to give0.773 g of a very light yellow solid. M.P. 140.0° C.

Insecticide and Miticide Utility

The compounds of formulas (1) and (1A) show activity against a number ofinsects and mites. More specifically, the compounds show activityagainst melon aphid, which is a member of the insect order Homoptera.Other members of the Homoptera include leafhoppers, planthoppers, pearpyslla, apple sucker, scale insects, whiteflies, spittle bugs as well asnumerous other host specific aphid species. Activity has also beenobserved against greenhouse thrips, which are members of the orderThysanoptera. The compounds also show activity against Southernarmyworm, which is a member of the insect order Lepidoptera. Othertypical members of this order are codling moth, cutworm, clothes moth,Indianmeal moth, leaf rollers, corn earworm, European corn borer,cabbage worm, cabbage looper, cotton bollworm, bagworm, eastern tentcaterpillar, sod webworm, and fall armyworm.

The compounds of formulas (1) and (1A) are useful for reducingpopulations of insects and mites, and are used in a method of inhibitingan insect or mite population which comprises applying to a locus of theinsect or mite an effective insect- or mite-inactivating amount of acompound of formula (1). The "locus" of insects or mites is a term usedherein to refer to the environment in which the insects or mites live orwhere their eggs are present, including the air surrounding them, thefood they eat, or objects which they contact. For example,plant-ingesting insects or mites can be controlled by applying theactive compound to plant parts, which the insects or mites eat,particularly the foliage. It is contemplated that the compounds mightalso be useful to protect textiles, paper, stored grain, or seeds byapplying an active compound to such substance. The term "inhibiting aninsect or mite" refers to a decrease in the numbers of living insects ormites; or a decrease in the number of viable insect or mite eggs. Theextent of reduction accomplished by a compound depends, of course, uponthe application rate of the compound, the particular compound used, andthe target insect or mite species. At least an insect-inactivating ormite-inactivating amount should be used. The terms "insect-inactivatingamount" and "mite-inactivating amount" are used to describe the amount,which is sufficient to cause a measurable reduction in the treatedinsect or mite population. Generally an amount in the range from about 1to about 1000 ppm active compound is used.

Some of the above identified compounds were tested for insecticidal,miticidal and nematicidal activity against eight species. Results arereported in the following table, wherein the following abbreviations areused:

ALH refers to aster leafhopper

BAW refers to beet armyworm

CA refers to cotton aphid

NEM refers to peanut rootknot nematode

SCRW refers to southern corn rootworm

TBW refers to tobacco budworm

TSSM refers to two spotted spider mite

GECR refers to German cockroach

In conducting evaluations of insecticidal activity, each test compoundwas formulated as a 400 ppm solution, and this solution was then dilutedwith water to give lesser concentrations. The 400 ppm solution wasprepared by combining 19.2 mL of 0.05% solution of Tween 20(polyoxyethylene (20) sorbitan monolaurate) in water with a solution of8 mg of the compound in 0.8 mL of acetone/EtOH (9/1).

Activity against aster leafhopper (Macrosteles fascifrons) was tested asfollows. The test was run using concentrations of 400 ppm and 50 ppm.One ounce plastic cups containing a cotton wick was sprayed with 0.4 mLof formulated material using a flat-fan nozzle. The excess moisture wasallowed to evaporate. Then five to ten carbon dioxide anesthetized adultleafhoppers were added to each cup. The cups were capped and held atroom temperature for 24 hours. Percent mortality was then determined.

Activity against beet armyworm (Spodoptera exiqua) was evaluated asfollows. The test is run using concentrations of 400 ppm and 50 ppm. Ageneral purpose lepidoptera artificial diet was diluted to half strengthwith a 5% non nutritive agar. 8 mL of this diet material was dispensedinto one ounce diet cups. One hour prior to treatment, 35 to 40 eggswere dispensed onto the diet surface. The cups were then sprayed withformulated material through a flat-fan nozzle. Treated cups were airdried prior to sealing with plastic caps. The cups were held for 6 daysat room temperature. Activity was then rated based on the total numberof live and dead larvae, and on the size of live larvae.

Activity against cotton aphid (Aphis gossypii) and two spotted spidermite (Tetranychus urticae) was evaluated as follows. Golden crooknecksquash plants were grown to the expanded cotyledon stage (about 6 to 8days). The plants were infested with cotton aphids and two spottedspider mites 16 to 24 hours before application of the test material bytransfer of infested foliage cut from a stock colony. Immediately priorto spray application of the test material the transfer foliage isremoved from the squash plants. The test is run using concentrations of400 ppm and 50 ppm. The plants are sprayed with test solution using anatomizing sprayer at 17 psi. Both surfaces of the leaves are covereduntil runoff, and then allowed to dry. Activity of each compound wasdetermined three days after treatment. Activity was rated as a percentbased on the mites/aphids present in plants sprayed with solvent alone.

Activity against peanut root knot nematode (Meloidogyne arenaria) wasevaluated as follows. Five untreated cucumber seeds are placed into thebottom of a clear one ounce cup, 20 g of clean white sand is added, andthe cups were sprayed while rotating on a pedestal allowing 1.0 mL of a400 ppm solution to be deposited on the sand. To each cup was dispensed2.5 to 3.0 mL of deionized water containing 300 to 500 nematodes. Thecups were held for 10 to 12 days in an environmental growth chamber at atemperature of 76° to 85° F. and ambient humidity of 50 to 60%. After 10to 12 days the cups were evaluated by inverting the cup and observingnematode mortality and feeding damage to the cucumber plants.

Activity on Southern corn rootworm (Diabrotica undecimpuctata howardiBarber) was evaluated by adding one mL of test solution containing apredetermined concentration of test compound to a cup containing akernel of corn in 16 g of sterile soil. This produces a soilconcentration of 24 ppm. After 1.5 to 2 hours of drying, five 4th instarcorn rootworm larvae were added to the individual cups. Mortality wasmeasured at 3-4 days by emptying the cup onto a pan and inspecting thesoil for live rootworms.

Activity against tobacco budworm (Heliothis virescens) was evaluated asfollows. A general purpose lepidoptera artificial diet was diluted tohalf strength with a 5% non nutritive agar. 8 mL of this diet materialwas dispensed into each one ounce diet cup. One hour prior to treatment18 to 20 eggs were dispensed onto the diet surface. The cups were thensprayed with formulated material through a flat-fan nozzle. The test wasrun using concentrations of 400 ppm and 50 ppm. Treated cups were airdried prior to sealing with plastic caps. The cups were held for 6 daysat room temperature. Activity was then rated based on the total numberof live and dead larvae, and on the size of live larvae.

Activity against German cockroach (Blattella germanicus) was evaluatedas follows. 8 mL of alfalfa based green insect diet material wasdispensed into a one ounce diet cup. The cups were then sprayed withformulated material through a flat-fan nozzle. The test was run usingconcentrations of 400 ppm and 50 ppm. Treated cups were air dried for 24hours and infested with five late third or early fourth instar Germancockroaches. The cups were capped and held for ten days in anenvironmental growth chamber at a temperature of 76°-85° C. Activity wasthen rated based on the total number of live and dead insects.

    __________________________________________________________________________    INSECTICIDE, MITICIDE, AND NEMATICIDE DATA                                          ALH  BAW  CA   NEM  SCRW TBW  TSSM GECR                                       400 ppm                                                                            400 ppm                                                                            400 ppm                                                                            400 ppm                                                                            400 ppm                                                                            400 ppm                                                                            400 ppm                                                                            400 ppm                              Compound                                                                            50 ppm                                                                             50 ppm                                                                             50 ppm                                                                             50 ppm                                                                             50 ppm                                                                             50 ppm                                                                             50 ppm                                                                             50 ppm                               __________________________________________________________________________     1    100  0    0         0    0    0    0                                          --   --   --        --   --   --   --                                    2                                                                             3                                                                             4    0    0    0         0    70   0    0                                          --   --   --        --   --   --   --                                    5         0    0         0    0    0    0                                               --   --        --   --   --   --                                    6         0    0         0    0    0    0                                               --   --        --   --   --   --                                    7    0    0    0         0    0    0    0                                          --   --   --        --   --   --   --                                    8    0    0    0         0    0    0    0                                          --   --   --        --   --   --   --                                    9    0    0    0         0    60   0    20                                         --   --   --        --   --   --   --                                   10    100  100  100  100  0    0    100  60                                         100  0    100  100  --   0    100  0                                    11    100  100  100  0    0    100  100  100                                        100  100  100  0    --   100  100  0                                    12    100  80   0    0    0    60   0    0                                          100  0    0    0    --   0    0    0                                    13    100  0    60   0    0    50   100  0                                          100  0    0    0    --   0    100  0                                    14    100  100  100  100  0    100  100  20                                         100  100  100  0    --   100  100  40                                   15    0    0    0    60   0    0    0    0                                          0    0    0    0    --   0    0    0                                    16    100  100  0    40   0    100  0    0                                          100  0    0    --   --   0    0    0                                    17    0    0    0    0    0    0    0    0                                          60   0    0    0    --   0    0    0                                    18    80   100  100  100  100  100  100  100                                        80   100  100  --   --   100  100  40                                   19    100  100  100  100  100  100  100  40                                         100  100  100  --   --   100  100  40                                   20    100  100  100  100  0    100  100  80                                         100  100  100  --   --   100  100  0                                    21    100  100  100  100  0    100  100  0                                          40   100  70   --   --   100  100  0                                    22    100  100  100  100  100  100  0    60                                         100  100  100  --   --   80   0    0                                    23    100  100  100  0    0    100  100  20                                         100  100  90   --   --   100  100  0                                    24    100  100  100  0    0    100  100  80                                         100  100  100  --   --   100  100  40                                   25    100  100  100  0    100  100  100  80                                         100  100  100  --   --   100  100  20                                   26    100  100  100  100  0    80   0    0                                          100  100  90   --   --   0    0    0                                    27    100  100  100  30   0    0    0    0                                          100  0    100  --   --   0    0    0                                    28    100  0    0    0    0    0    0    0                                          100  0    0    0    --   0    0    0                                    29    100  100  100  0    0    100  100  0                                          100  100  100  --   --   100  100  0                                    30    100  100  100  100  100  100  100  100                                        100  100  100  --   --   100  100  60                                   31    100  100  100  0    100  100  100  40                                         100  100  100  --   --   100  100  0                                    32    80   100  0    0    100  100  0    0                                          60   100  0    --   --   100  0    0                                    33    100  100  100  0    0    80   100  0                                          100  100  0    --   --   40   0    20                                   34    100  100  100  100  100  100  100  100                                        100  100  100  --   --   100  100  60                                   35    80   0    0    0    0    0    0    20                                         80   0    0    --   --   0    0    0                                    36    100  100  100  100  100  100  100  100                                        100  100  100  --   --   100  100  100                                  37    100  100  100  100  100  100  100  100                                        100  100  100  --   --   100  100  100                                  38    100  100  100  100  100  100  100  100                                        100  100  100  --   --   100  100  100                                  39    100  100  100  100  100  100  100  0                                          100  100  100  --   --   100  100  0                                    40    100  100  100  0    100  100  100  100                                        100  100  100  --   --   100  100  80                                   41    --   --   --   --   --   --   --   --                                         --   --   --   --   --   --   --   --                                   42    100  0    100  0    0    0    100  --                                         100  0    100  --   --   0    100  --                                   43    100  100  0    0    0    100  0    --                                         100  100  0    --   --   100  0    --                                   44    100  100  100  0    100  100  100  --                                         100  100  100  --   --   100  100  --                                   45    100  100  100  0    100  100  100  --                                         100  100  100  --   --   100  0    --                                   46    100  100  100  0    0    100  100  --                                         100  100  100  --   --   0    100  --                                   47    100  100  100  0    0    100  100  --                                         100  100  100  --   --   100  100  --                                   48    100  100  100  0    0    100  100  --                                         100  100  100  --   --   100  100  --                                   49    100  100  100  0    0    100  0    --                                         100  10   100  --   --   100  0    --                                   50    100  100  100  0    100  100  100  --                                         100  100  100  --   --   100  100  --                                   51    100  100  100  0    100  100  100  --                                         100  100  100  --   --   100  100  --                                   52    100  100  0    0    0    100  0    --                                         100  100  0    --   --   100  0    --                                   53                                                                            54                                                                            55                                                                            56    100  100  100  0    0    100  100  60                                         100  100  100  0    0    100  100  0                                    57    100  100  100  0    0    100  100  0                                          60   100  100  --   --   100  90   0                                    58    60   100  0    100  0    100  0    0                                          80   100  0    --   --   100  0    0                                    59    100  100  100  100  100  100  100  0                                          100  100  100  --   --   100  100  0                                    60    100  100  100  0    0    60   0    --                                         80   100  100  --   --   0    0    --                                   61    100  100  100            100  100                                             100  100  100            0    100                                       62    100  100  100  100       100  100                                             100  100  100  0         100  100                                       63    100  100  100  0    0    100  90                                              100  70   100  0    0    100  80                                        64    100  100  100  0    100  100  100                                             100  100  100  0    0    100  100                                       __________________________________________________________________________

Mite-Insect Screen

Some of the above identified compounds were tested for miticidal andinsecticidal activity in the following mite/insect screen.

Each test compound was formulated as a 400 ppm solution, and thissolution was then diluted with water to give the indicatedconcentrations. The 400 ppm solution was prepared by combining 19.2 mLof 0.05% solution of Tween 20 (polyoxyethylene (20) sorbitanmonolaurate) in water with a solution of 8 mg of the compound in 0.8 mLof acetone/EtOH (9/1).

Twospotted spider mites (Tetranychus urticae Koch) and melon aphids(Aphis gossypii Glover) are introduced on squash cotyledons and allowedto establish on both leaf surfaces. Other plants in the same treatmentpot are left uninfested. The leaves are then sprayed with test solutionusing an atomizing sprayer at 17 psi. Both surfaces of the leaves arecovered until runoff, and then allowed to dry. Activity of a compound isdetermined 48 hours after treatment. Activity is rated as a percentbased on the mites/aphids present in plants sprayed with solvent alone.An uninfested plant is cut after the spraying and drying steps andplaced into a Petri dish containing larval southern armyworm (Spodopetraeridania Cramer). The larvae are checked after 72 to 96 hours formortality and for antifeedent activity of the compound. The ratings arebased on comparison to results on plants sprayed with solvent alone.

Activity on Southern corn rootworm (Diabrotica undecimpuctata howardiBarber) is evaluated by adding one mL of test solution containing apredetermined concentration of test compound to a cup containing akernel of corn in 16 g of sterile soil. This produces a soilconcentration of 24 ppm. After 1.5 to 2 hours of drying, five 4th instarcorn rootworm larvae are added to the individual cups. Mortality ismeasured at 3-4 days by emptying the cup onto a pan and inspecting thesoil for live rootworms.

Results are reported in the following table. The following abbreviationsare used in the table:

CRW refers to corn rootworm

SAW refers to Southern armyworm

SM refers to twospotted spider mites

MA refers to melon aphids.

    __________________________________________________________________________                      SAW                                                                 CRW CRW   SM & MA                                                                             SAW   SM    MA                                                RATE                                                                              RESULTS                                                                             RATE  RESULTS                                                                             RESULTS                                                                             RESULTS                                   COMPOUND                                                                              PPM %     PPM   %     %     %                                         __________________________________________________________________________    1A      12.00                                                                             0     200   0     0     0                                                 24.00                                                                             0     400   0     80    100                                       2A      12.00                                                                             0     200   0     90    60                                                24.00                                                                             0     400   0     0     0                                         3A      12.00                                                                             0     200   0     0     0                                                 24.00                                                                             0     400   0     0     0                                         4A      12.00                                                                             0     200   0     90    90                                                24.00                                                                             0     400   0     80    100                                       5A      12.00                                                                             0     200   0     100   100                                               24.00                                                                             0     400   0     0     0                                         6A      12.00                                                                             0     200   0     0     0                                                 24.00                                                                             0     400   0     0     0                                         7A      12.00                                                                             0     200   0     50    90                                                24.00                                                                             0     400   0     80    80                                        8A      12.00                                                                             0     200   0     100   100                                               24.00                                                                             0     400   0     90    70                                        9A      12.00                                                                             0     200   0     100   100                                               24.00                                                                             0     400   60    100   100                                       10A     12.00                                                                             0     200   0     60    90                                                24.00                                                                             0     400   0     80    50                                        12A     12.00                                                                             0     200   0     0     0                                                 24.00                                                                             0     400   0     0     0                                         13A     12.00                                                                             0     200   0     0     0                                                 24.00                                                                             0     400   0     0     0                                         __________________________________________________________________________

Nematicide Utility

The compounds of the present invention are particularly useful forreducing populations of nematodes. Accordingly, a significant aspect ofthe invention is a method of inhibiting a nematode population whichcomprises applying to a locus of a nematode an effective nematodeinactivating amount of a compound of formula (1) or (1A). The term"inhibiting a nematode" refers to a decrease in the numbers of livingnematodes. The extent of reduction accomplished by a compound dependsupon the application rate of the compound, the particular compound used,and the target species. At least a nematode-inactivating amount shouldbe used. The term "nematode-inactivating amount" is used to describe theamount, which is sufficient to cause a measurable reduction in thetreated nematode population.

The method is practiced in accordance with standard techniques for theapplication of nematicides. In general, good nematicidal activity can beexpected at rates of 1-10 lbs/acre. The compound can be formulated asdescribed below in the Compositions section. When formulated asdispersions, nematicides are typically applied as aqueous drenchesaround growing plants or applied incrementally via irrigation systems.When applied as granules, nematicides may be incorporated into the soilbefore planting, or applied in a band on top of a seed row, or broadcastand then incorporated into the soil, or used as a side dressing to anestablished crop.

Compounds showing promising activity in the mite insect screen that isdescribed above were tested against the peanut root knot nematode,Meloidogyne arenaria, in the peanut root knot nematode assay. In thistest a 200 ppm solution of each test compound is prepared by dilutingwith water the 400 ppm used in the mite insect screen. Three to fourcucumber seeds are placed in 16 g of clean white sand, and 1 mL of the200 ppm solution of test compound is added. This provides aconcentration of the compound in the soil of 12 ppm. The cups areallowed to dry one to two hours, and then one mL of a concentrated (50to 60 per mL) nematode (Meloidogyne arenaria) suspension is added toeach cup. The cups are incubated for four to seven days. Then 11 mL ofdeionized water is added to each cup and the cup is gently shaken torinse the nematodes from the sand. The suspension is poured into awatchglass and observed under a dissecting microscope at 15×-20×. Anactivity rating is given based on nematode mortality. Aldicarb,carbofuran, and fenamiphos are used as chemical standard compounds.Results are reported in the following table.

    ______________________________________                                                                 Nematode                                                           Rate       Results                                              Compound      ppm in sand                                                                              % control                                            ______________________________________                                        1A            12.00      0.00                                                 2A            12.00      100.00                                               3A            12.00      100.00                                               5A            12.00      0.00                                                 6A            12.00      100.00                                               7A            12.00      0.00                                                 8A            12.00      100.00                                               9A            12.00      100.00                                               10A           12.00      100.00                                               12A           24.00      0.00                                                 13A           24.00      0.00                                                 ______________________________________                                    

Other compounds were tested against the peanut root knot nematode,Meloidogyne arenaria, in a similar standardized screening test in whichfive untreated cucumber seeds are placed into the bottom of a clear onounce cup, 20 g of clean white sand is added, and the cups are sprayedwhile rotating on a pedestal allowing 1.0 mL of a 400 ppm solution (asused in the mite insect screen described above) to be deposited on thesand. To each cup is dispensed 2.5 to 3.0 mL of deionized watercontaining 300 to 500 nematodes. The cups are held for 10 to 12 days inan environmental growth chamber at a temperature of 76° to 85° F. andambient humidity of 50 to 60%. After 10 to 12 days the cups areevaluated by inverting the cup and observing nematode mortality andfeeding damage to the cucumber plants. Results are reported in thefollowing table.

    ______________________________________                                                      Nematode                                                                      Results                                                         Compound      % control                                                       ______________________________________                                        15A           0.00                                                            17A           0.00                                                            20A           100.00                                                          21A           0.00                                                            22A           0.00                                                            23A           0.00                                                            ______________________________________                                    

Fungicide Utility

The compounds of the present invention have been found to control fungi,particularly plant pathogens. When employed in the treatment of plantfungal diseases, the compounds are applied to the plants in a diseaseinhibiting and phytologically acceptable amount. The term "diseaseinhibiting and phytologically acceptable amount," as used herein, refersto an amount of a compound of the invention which kills or inhibits theplant disease for which control is desired, but is not significantlytoxic to the plant. This amount will generally be from about 1 to 1000ppm, with 10 to 500 ppm being preferred. The exact concentration ofcompound required varies with the fungal disease to be controlled, thetype formulation employed, the method of application, the particularplant species, climate conditions and the like. A suitable applicationrate is typically in the range from 0.25 to 4 lb/A. The compounds of theinvention may also be used to protect stored grain and other non-plantloci from fungal infestation.

Greenhouse Tests

The following experiments were performed in the laboratory to determinethe fungicidal efficacy of the compounds of the invention.

The test compounds were formulated for application by dissolving 50 mgof the compound into 1.25 ml of solvent. The solvent was prepared bymixing 50 ml of "Tween 20" (polyoxyethylene (20) sorbitan monolaurateemulsifier) with 475 ml of acetone and 475 ml of ethanol. Thesolvent/compound solution was diluted to 125 ml with deionized water.The resulting formulation contains 400 ppm test chemical. Lowerconcentrations were obtained by serial dilution with thesolvent-surfactant mixture.

The formulated test compounds were applied by foliar spray. Thefollowing plant pathogens and their corresponding plants were employed.

    ______________________________________                                                          Designation                                                                   in following                                                Pathogen          Table        Host                                           ______________________________________                                        Erysiphe graminis tritici                                                                       ERYSGT       wheat                                          (powdery mildew)                                                              Pyricularia oryzae (rice                                                                        PYRIOR       rice                                           blast)                                                                        Puccinia recondita                                                                              PUCCRT       wheat                                          tritici (leaf rust)                                                           Leptosphaeria nodorum                                                                           LEPTNO       wheat                                          (glume blotch)                                                                Plasmopara viticola                                                                             PLASVI       grape                                          (downy mildew)                                                                ______________________________________                                    

The formulated technical compounds were sprayed on all foliar surfacesof the host plants (or cut berry) to past run-off. Single pots of eachhost plant were placed on raised, revolving pedestals in a fume hood.Test solutions were sprayed on all foliar surfaces. All treatments wereallowed to dry and the plants were inoculated with the appropriatepathogens within 2-4 hours.

The following table presents the activity of typical compounds of thepresent invention when evaluated in this experiment. The effectivenessof test compounds in controlling disease was rated using the followingscale.

0=not tested against specific organism

-=0-19% control at 400 ppm

+=20-89% control at 400 ppm

++=90-100% control at 400 ppm

+++=90-100% control at 100 ppm

    __________________________________________________________________________    COMPOUND NUMBER                                                                            ERYSGT                                                                              PYRIOR                                                                             PUCCRT                                                                              LEPTNO                                                                              PLASVI                                    __________________________________________________________________________     1           -     -    -     -     +                                          2           ++    -    -     0     0                                          3           -     -    +++   -     ++                                         4           +     +    +     -     +++                                        5           -     -    ++    -     -                                          6           +     +    +     -     +                                          7           -     -    +     -     -                                          8           +     -    +     -     +                                          9           +     +    ++    0     0                                         10           ++    +    +++   ++    +++                                       11           +++   ++   +++   ++    ++                                        12           ++    +    ++    -     +                                         13           ++    ++   +++   -     ++                                        14           + ++  +++  +++   ++    +++                                       15           -     +    +     +     ++                                        16           +++   ++   +++   ++    +++                                       17           -     -    -     -     -                                         18           +++   +++  +++   ++    +++                                       19           +++   +++  +++   ++    +++                                       20           +++   +++  +++   -     +++                                       21           ++    ++   ++    ++    ++                                        22           ++    +    ++    +     +++                                       23           ++    +    ++    +     +++                                       24           ++    +    ++    +     +++                                       25           +     +    ++    +     +++                                       26           ++    ++   ++    +     ++                                        27           ++    +    +     ++    ++                                        28           ++    -    ++    +++   ++                                        29           +++   +++  ++    +     +++                                       30           +++   +++  ++    +++   +++                                       31           +++   ++   ++    ++    ++                                        32           +++   +    ++    ++    ++                                        33           +++   +    ++    +     ++                                        34           +++   ++   ++    +++   +++                                       35           ++    +    ++    ++    ++                                        36           ++    +    ++    +     ++                                        37           ++    +    ++    ++    +                                         38           ++    +    ++    ++    +                                         39           -     -    ++    +     -                                         40           ++    +    ++    ++    ++                                        41           +++   +++  ++    ++    ++                                        42           ++    ++   ++    ++    ++                                        43           +++   ++   -     +++   +++                                       44           ++    ++   ++    ++    -                                         45           ++    +    ++    ++    ++                                        46           ++    +    ++    ++    +                                         47           ++    -    ++    -     ++                                        48           ++    ++   ++    -     ++                                        49           +     -    ++    +     -                                         50           ++    ++   ++    ++    ++                                        51           ++    ++   ++    ++    ++                                        52           +     +    ++    +     -                                         53                                                                            54                                                                            55                                                                            56           +++   ++   0     ++    +++                                       57           +++   -    0     -     +++                                       58           +++   +    0     +     +                                         59           +++   ++   0     +     +++                                       60           +     -    0     -     +                                         61           -     -    0     -     +++                                       62           +     -    0     +     +++                                       63           +     +++  0     ++    +++                                       64           +++   +    0     ++    +++                                         1A         +     -    +                                                       2A         +     -    -                                                       3A         -     -    +                                                       4A         +     +    +                                                       5A         -     -    -                                                       6A         -     -    -                                                       7A         -     ++   +                                                       8A         +     +    -                                                       9A         +     -    -                                                       10A        +     +    +                                                       11A        -     -    -                                                       12A        -     -    -                                                       13A        +     -    +                                                       14A        +     -    +                                                       16A        -     -    -                                                       20A        +     ++   ++                                                      21A        -     -    +                                                       22A        +     -    +                                                       23A        +     -    -                                                     __________________________________________________________________________

Compositions

The compounds of formula (1) and (1A) are applied in the form ofcompositions which are important embodiments of the invention, and whichcomprise a compound of formula (1) or (1A) and aphytologically-acceptable inert carrier. The compositions are eitherconcentrated formulations which are dispersed in water for application,or are dust or granular formulations which are applied without furthertreatment. The compositions are prepared according to procedures andformulae which are conventional in the agricultural chemical art, butwhich are novel and important because of the presence therein of thecompounds of this invention. Some description of the formulation of thecompositions will be given, however, to assure that agriculturalchemists can readily prepare any desired composition.

The dispersions in which the compounds are applied are most oftenaqueous suspensions or emulsions prepared from concentrated formulationsof the compounds. Such water-soluble, water-suspendable or emulsifiableformulations are either solids usually known as wettable powders, orliquids usually known as emulsifiable concentrates or aqueoussuspensions. Wettable powders, which may be compacted to form waterdispersible granules, comprise an intimate mixture of the activecompound, an inert carrier and surfactants. The concentration of theactive compound is usually from about 10% to about 90% by weight. Theinert carrier is usually chosen from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among the sulfonated lignins, thecondensed naphthalenesulfonates, the naphthalenesulfonates, thealkylbenzenesulfonates, the alkyl sulfates, and non-ionic surfactantssuch as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of the compounds comprise a convenientconcentration of a compound, such as from about 50 to about 500 gramsper liter of liquid, equivalent to about 10% to about 50%, dissolved inan inert carrier which is either a water miscible solvent or a mixtureof water-immiscible organic solvent and emulsifiers. Useful organicsolvents include aromatics, especially the xylenes, and the petroleumfractions, especially the high-boiling naphthalenic and olefinicportions of petroleum such as heavy aromatic naphtha. Other organicsolvents may also be used, such as the terpenic solvents including rosinderivatives, aliphatic ketones such as cyclohexanone, and complexalcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiableconcentrates are chosen from conventional nonionic surfactants, such asthose discussed above.

Aqueous suspensions comprise suspensions of water-insoluble compounds ofthis invention, dispersed in an aqueous vehicle at a concentration inthe range from about 5% to about 50% by weight. Suspensions are preparedby finely grinding the compound, and vigorously mixing it into a vehiclecomprised of water and surfactants chosen from the same types discussedabove. Inert ingredients, such as inorganic salts and synthetic ornatural gums, may also be added, to increase the density and viscosityof the aqueous vehicle. It is often most effective to grind and mix thecompound at the same time by preparing the aqueous mixture, andhomogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

The compounds may also be applied as granular compositions, which areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the compound,dispersed in an inert carrier which consists entirely or in large partof clay or a similar inexpensive substance. Such compositions areusually prepared by dissolving the compound in a suitable solvent, andapplying it to a granular carrier which has been pre-formed to theappropriate particle size, in the range of from about 0.5 to 3 mm. Suchcompositions may also be formulated by making a dough or paste of thecarrier and compound, and crushing and drying to obtain the desiredgranular particle size.

Dusts containing the compounds are prepared simply by intimately mixingthe compound in powdered form with a suitable dusty agriculturalcarrier, such as kaolin clay, ground volcanic rock and the like. Dustscan suitably contain from about 1% to about 10% of the compound.

It is equally practical, when desirable for any reason, to apply thecompound in the form of a solution in an appropriate organic solvent,usually a bland petroleum oil, such as the spray oils, which are widelyused in agricultural chemistry.

Insecticides and miticides are generally applied in the form of adispersion of the active ingredient in a liquid carrier. It isconventional to refer to application rates in terms of the concentrationof active ingredient in the carrier. The most widely used carrier iswater.

The compounds of formula (1) can also be applied in the form of anaerosol composition. In such compositions the active compound isdissolved or dispersed in an inert carrier, which is apressure-generating propellant mixture. The aerosol composition ispackaged in a container from which the mixture is dispensed through anatomizing valve. Propellant mixtures comprise either low-boilinghalocarbons, which may be mixed with organic solvents, or aqueoussuspensions pressurized with inert gases or gaseous hydrocarbons.

The actual amount of compound to be applied to loci of insects and mitesis not critical and can readily be determined by those skilled in theart in view of the examples above. In general, concentrations of from 10ppm to 5000 ppm of compound are expected to provide good control. Withmany of the compounds, concentrations of from 100 to 1500 ppm willsuffice. For field crops, such as soybeans and cotton, a suitableapplication rate for the compounds is about 0.5 to 1.5 lb/A, typicallyapplied in 50 gal/A of spray formulation containing 1200 to 3600 ppm ofcompound. For citrus crops, a suitable application rate is from about100 to 1500 gal/A spray formulation, which is a rate of 100 to 1000 ppm.

The locus to which a compound is applied can be any locus inhabited byan insect or arachnid, for example, vegetable crops, fruit and nuttrees, grape vines, and ornamental plants. Inasmuch as many mite speciesare specific to a particular host, the foregoing list of mite speciesprovides exemplification of the wide range of settings in which thepresent compounds can be used.

Because of the unique ability of mite eggs to resist toxicant action,repeated applications may be desirable to control newly emerged larvae,as is true of other known acaricides.

The following formulations of compounds of the invention are typical ofcompositions useful in the practice of the present invention.

    ______________________________________                                        A. 0.75 Emulsifiable Concentrate                                              Compound of formula (1) or (1A)                                                                       9.38%                                                 "TOXIMUL D"             2.50%                                                 (nonionic/anionic surfactant blend)                                           "TOXIMUL H"             2.50%                                                 (nonionic/anionic surfactant blend)                                           "EXXON 200"             85.62%                                                (naphthalenic solvent)                                                        B. 1.5 Emulsifiable Concentrate                                               Compound of formula (1) or (1A)                                                                       18.50%                                                "TOXIMUL D"             2.50%                                                 "TOXIMUL H"             2.50%                                                 "EXXON 200"             76.50%                                                C. 1.0 Emulsifiable Concentrate                                               Compound of formula (1) or (1A)                                                                       12.50%                                                N-methylpyrrolidone     25.00%                                                "TOXIMUL D"             2.50%                                                 "TOXIMUL H"             2.50%                                                 "EXXON 200"             57.50%                                                D. 1.0 Aqueous Suspension                                                     Compound of formula (1) or (1A)                                                                       12.00%                                                "PLURONIC P-103"        1.50%                                                 (block copolymer of propylene oxide                                           and ethylene oxide, surfactant)                                               "PROXEL GXL"            .05%                                                  (biocide/preservative)                                                        "AF-100"                .20%                                                  (silicon based antifoam agent)                                                "REAX 88B"              1.00%                                                 (lignosulfonate dispersing agent)                                             propylene glycol        10.00%                                                veegum                  .75%                                                  xanthan                 .25%                                                  water                   74.25%                                                E. 1.0 Aqueous Suspension                                                     Compound of formula (1) or (1A)                                                                       12.50%                                                "MAKON 101" (10 moles ethyleneoxide                                                                   1.00%                                                 nonylphenol surfactant)                                                       "ZEOSYL 200" (silica)   1.00%                                                 "AF-100"                0.20%                                                 "AGRIWET FR" (surfactant)                                                                             3.00%                                                 2% xanthan hydrate      10.00%                                                water                   72.30%                                                F. 1.0 Aqueous Suspension                                                     Compound of formula (1) or (1A)                                                                       12.50%                                                "MAKON 10"              1.50%                                                 "ZEOSYL 200" (silica)   1.00%                                                 "AF-100"                0.20%                                                 "POLYFON H"             0.20%                                                 (lignosulfonate dispersing agent)                                             2% xanthan hydrate      10.00%                                                water                   74.60%                                                G. Wettable Powder                                                            Compound of formula (1) or (1A)                                                                       25.80%                                                "POLYFON H"             3.50%                                                 "SELLOGEN HR"           5.00%                                                 "STEPANOL ME DRY"       1.00%                                                 gum arabic              0.50%                                                 "HISIL 233"             2.50%                                                 Barden clay             61.70%                                                H. Granules                                                                   Compound of formula (1) or (1A)                                                                       5.0%                                                  propylene glycol        5.0%                                                  Exxon 200               5.0%                                                  Florex 30/60 granular clay                                                                            85.0%                                                 ______________________________________                                    

We claim:
 1. A compound of the formula: ##STR116## or an N-oxide or asalt thereof, wherein R¹ is H or F;Y' is CH₂ ;a phenyl group optionallysubstituted with one or two groups independently selected from: halo,phenoxy, optionally substituted with one or two groups selected fromhalo, CN, NO₂, C₁ -C₄ -alkoxy, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl; phenyl,C₁ -C₅ alkyl, straight chain or branched, C₁ -C₄ haloalkyl; C₁ -C₄alkoxy; C₃ -C₇ branched alkoxy; halo (C₁ -C₄) alkoxy; halo (C₃ -C₇)branched alkoxy.
 2. N-(8-fluoro-4-quinolinyl) (4-((4-chlorophenyl)oxy)phenyl)acetamide.
 3. A pesticide composition which comprises aneffective amount of a compound of claim 1 in combination with anagriculturally acceptable carrier.
 4. A method of inhibiting an insector mite population which comprises applying to the locus of the insector arachnid an effective insect or mite inactivating amount of acompound of claim
 1. 5. A method of inhibiting a nematode populationwhich comprises applying to the locus of a nematode, an amount of acompound of claim 1 effective to inactivate nematodes.
 6. A method ofinhibiting plant pathogens which comprises applying an effective amountof a compound of claim 1 to a locus of the pathogen.